New insights into cancer pathology learned from the dynamics of cancer-associated fibroblasts

Paget's "Seed and Soil" theory, proposed in 1889, emphasizes the importance of the microenvironment where cancer cells grow in metastatic sites. Over a century later, this concept remains a cornerstone in comprehending cancer biology and devising treatment strategies. The "Seed and Soil" theory, which initially explained how cancer spreads to distant organs, now also applies to the tumor microenvironment (TME) within primary tumors. This theory emphasizes the critical interaction between cancer cells ("seeds") and their surrounding environment ("soil") and how this interaction affects both tumor progression within the primary site and at metastatic sites. An important point to note is that the characteristics of the TME are not static but dynamic, undergoing substantial changes during tumor progression and after treatment with therapeutic drugs. Cancer-associated fibroblasts (CAFs), recognized as the principal noncancerous cellular component within the TME, play multifaceted roles in tumor progression including promoting angiogenesis, remodeling the extracellular matrix, and regulating immune responses. In this comprehensive review, we focus on the findings regarding how the dynamics of CAFs contribute to cancer progression and drug sensitivity. Understanding the dynamics of CAFs could provide new insights into cancer pathology and lead to important advancements in cancer research and treatment.